Immunogenic tumors such as the murine meth A fibrosarcoma, characteristically have a peripheral zone which contains a chronic inflammatory infiltry (Dvorak, H., New Engl. J. Med., 315:1650-1658 (1986)). The presence of these inflammatory cells, often embedded in a mesh work of fibrin which can extend throughout the tumor stroma, contributes to the concept that tumors might be considered wounds that do not heal (Id.). There have been identified tumor-derived mediators which prime the host response, altering endothelial properties, and attracting inflammatory cells to the tumor. Empa I is a trypsin-sensitive, approximately 40 kDa polypeptide distinct from other cytokines and growth factors, and which could activate endothelial cells and monocytes. Another polypeptide has been identified which is the murine homologue of vpf/vegf, a factor which had previously been shown to increase vascular permeability and to be mitogenic for endothelial cells. Recently, another polypeptide has been identified in supernatants of meth A tumor cells (EMAP II). EMAP II activates endothelial cells (ECs) and mononuclear cells potentiating their participation in procoagulant reactions through induction of tissue factor, promoting migration of monocytes and polymorphonuclear leukocytes, and leading to a phlogogenic response when injected into murine foot pads. EMAP II is an apparently unique polypeptide which runs as a broad band.
The polypeptide of the present invention has been putatively identified as a EMAP III as a result of amino acid sequence homology to EMAP II.
In accordance with one aspect of the present invention, there is provided a novel mature polypeptide, as well as biologically active and diagnostically or therapeutically useful fragments, analogs and derivatives thereof. The polypeptide of the present invention is of human origin.
In accordance with another aspect of the present invention, there are provided isolated nucleic acid molecules encoding a polypeptide of the present invention including mRNAs, DNAs, cDNAs, genomic DNAs as well as analogs and biologically active and diagnostically or therapeutically useful fragments thereof.
In accordance with yet a further aspect of the present invention, there is provided a process for producing such polypeptide by recombinant techniques comprising culturing recombinant prokaryotic and/or eukaryotic host cells, containing a nucleic acid sequence encoding a polypeptide of the present invention, under conditions promoting expression of said protein and subsequent recovery of said protein.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptide, or polynucleotide encoding such polypeptide for therapeutic purposes, for example, neoplasia such as tumors in cancer.
In accordance with yet a further aspect of the present invention, there are provided antibodies against such polypeptides.
In accordance with another aspect of the present invention, there are provided agonists which mimic EMAP III and bind to the EMAP III receptors to elicit responses.
In accordance with yet a further aspect of the present invention, there is also provided nucleic acid probes comprising nucleic acid molecules of sufficient length to specifically hybridize to a nucleic acid sequence of the present invention.
In accordance with still another aspect of the present invention, there are provided diagnostic assays for detecting diseases or susceptibility to diseases related to mutations in the nucleic acid sequences encoding a polypeptide of the present invention.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or polynucleotides encoding such polypeptides, for in vitro purposes related to scientific research, for example, synthesis of DNA and manufacture of DNA vectors.
These and other aspects of the present invention should be apparent to those skilled in the art from the teachings herein.